A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome

Inclusion Criteria:

- Histologically or cytologically confirmed acute myeloid leukemia (AML)
ormyelodysplastic syndromes meeting 1 of the following criteria:

- Relapsed AML meeting any of the following criteria:

- Good-risk cytogenetics (inv[16], t[8;21], or t[15;17]) in second orgreater
relapse

- Patients with AML t(15;17) must have failed prior tretinoin and
arsenic-containing regimens AND progressed orrelapsed within 12
months of therapy

- In first or greater relapse

- Resistant AML

- Unable to achieve first complete remission after at least 2
inductionregimens

- Untreated AML meeting any of the following criteria:

- At least 60 years of age

- Preceding MDS

- MDS

- International Prognosis Scoring System (IPSS) risk groupof intermediate-2
or higher

- Patients with relapsed disease after allogeneic hematopoietic stem cell
transplantation (HSCT) must be off allimmunosuppressive medications for at least 30
days and have no symptoms orsigns of graft-vs-host disease

- No active CNS metastasis

- Patients with clinical signs of CNS disease or a history of CNS diseasewithin
the past 6 months are required to undergo lumbar puncture to excludeCNS
involvement

- No symptomatic leukostasis or requirement for leukapheresis

- Not eligible for allogeneic HSCTAND no suitable donor at the time of study entry

- Patients who areeligible for HSCT, informed of the option, and choose not to
proceed to HSCTare allowed

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Bilirubin normal

- AST and/or ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- No proteinuria ≥ 1+ on 2 consecutive urinalysis taken ≥ 1 week apart

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No HIV positivity

- LVEF ≥ 45% by echocardiography

- Mean QTc ≤ 500 msec (with Bazett's correction)

- No other significant ECG abnormality

- No history of familial long QT syndrome

- No disseminated intravascular coagulation

- No history of allergic reactions attributed to compounds of similar chemical
orbiological composition to AZD2171

- No concurrent uncontrolled illness, including, but not limited to, any of the
following:

- Hypertension

- Thyroid disease

- Ongoing or active infection

- Symptomatic congestive heartfailure

- Unstable angina pectoris

- Cardiac arrhythmia

- NYHA class III-IV heart disease

- NYHA class II heart disease controlled with treatment allowed

- Psychiatric illness or social situations that would limit study compliance

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy (6 weeks fornitrosoureas or mitomycin C),
radiotherapy, or major surgery and recovered

- Hydroxyurea allowed to control peripheral blast count> 20,000/mcL prior to study
entry and during the first 3 days of study therapy

- More than 4 weeks since prior and no concurrent growth factor or other cytokine
support

- At least 30 days since prior investigational agents or participation in
aninvestigational trial

- No more than 3 prior courses of induction chemotherapy

- Induction chemotherapyis defined as that intended to induce complete remission
and given at a time thatthe patient has active disease

- No concurrent CYP interactive medications

- No other concurrent investigational agents

- No concurrent drugs or biologics with proarrhythmic potential

- Prior and concurrent hydroxyurea allowed to control peripheral blast count>
20,000/mcL during the first 3 days of study therapy